215P - Differential spatial gene expression and clinicopathologic characteristics are associated with exceptional response to immune checkpoint inhibition in recurrent/metastatic head and neck cancer

Background

Immunotherapy (IO) using programmed cell death protein 1 inhibitors is the standard of care in recurrent/metastatic head and neck cancer (R/M HNSCC). While response rate is almost 20% in the total population, a small percentage of patients shows exceptional response. Here, spatial whole transcriptome data were analysed to investigate potential compartment-specific associations of RNA expression with exceptional response to (IO).

Methods

Prospectively collected pre-treatment biopsies and clinicopathologic data of 50 IO-treated patients with R/M HNSCC were included in the study. Exceptional response (ER) was defined as complete or partial response (RECIST 1.1), lasting longer than 3 times the median response duration found in literature for the same treatment setting. Samples were evaluated using the GeoMx Human Whole Transcriptome Atlas (NanoString) assay for the in-situ quantification of 18,677 genes in the tumor (CK), leukocyte (CD45) and macrophage (CD68) tissue compartments. Differentially expressed genes (P<0.05, FDR 0.05) between ER and non-ER cases were identified in each compartment. Immune cell genes extracted from the “Single Cell RNA-Seq HNSCC” (CIBERSORTx) gene matrix and clinicopathologic characteristics; smoking, alcohol, sex, age, primary site and PD-L1 status, were investigated for correlations with ER.

Results

Seven exceptional responders were identified. Five immunoglobulin (Ig) genes (IGHG1, IGHG2, IGHG3, IGHG4, IGLL5) and one B-cell related gene (MZB1) showed the highest expression for exceptional responders both in the CD45 and CD68 compartments (stroma). Follicular dendritic cell secreted protein gene (FDCSP) was highly expressed in tumor. There was no association of ER with the immune-cell phenotypes derived from CIBERSORTx deconvolution. Alcohol consumption was the only clinicopathologic characteristic that showed association with ER (P=0.047).

Conclusions

ER to IO in R/M HNSCC is characterized by increased expression of Ig and B-cell related genes in tumor and stroma, indicating the importance of secreted immune factors for durable IO responses.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Rimm: Financial Interests, Personal, Advisory Board: AstraZeneca, Agendia, Cell Signaling Technology, Amgen, BMS, Cepheid, Danaher, Daiichi Sankyo, Genoptix/Novartis, Konica/Minolta, GSK, Merck, NanoString, PAIGE.AI, Perkin Elmer, Roche, Sanofi, Ventana; Financial Interests, Institutional, Funding: Amgen, Cepheid, NavigateBP, NextCure, Konica/Minolta. A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono, EPICS; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, Leo, Rakuten, eTheRNA immunotherapies, Merck Serono, Seagen, Merus, Merus Pharmaceuticals, GSK; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Pfizer, GSK, Genesis, Incyte, Amgen, Debiopharm, MSD, Janssen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Iovance, Pfizer, Roche; Financial Interests, Institutional, Steering Committee Member: Kura Oncology; Financial Interests, Personal, Steering Committee Member: Kura Oncology, GSK, Merus Pharmaceuticals; Financial Interests, Personal and Institutional, Funding: Kura Oncology, BMS, Roche, DEMO, Amgen, BI, Genesis, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer, GSK; Financial Interests, Personal, Other, Educational activity: Medscape, Prime Oncology; Financial Interests, Institutional, Local PI: Novartis, Replimune. All other authors have declared no conflicts of interest.